rs1897604

Positions:

• chr19-50944698-T-C
• chr19-50944698-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012427.5(KLK5):​c.727-912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,124 control chromosomes in the GnomAD database, including 8,041 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (8041 hom., cov: 32)
• Consequence: KLK5 NM_012427.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

KLK5 (HGNC:6366): (kallikrein related peptidase 5) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its expression is up-regulated by estrogens and progestins. The encoded protein is secreted and may be involved in desquamation in the epidermis. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

KLK5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK5	NM_012427.5	c.727-912A>G		intron_variant		ENST00000336334.8	NP_036559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK5	ENST00000336334.8	c.727-912A>G		intron_variant		1	NM_012427.5	ENSP00000337733.2
KLK5	ENST00000391809.6	c.727-912A>G		intron_variant		1		ENSP00000375685.1
KLK5	ENST00000593428.5	c.727-912A>G		intron_variant		1		ENSP00000471966.1
KLK5	ENST00000595585.1	n.823-912A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45077 AN: 152006 Hom.: 8025 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45117 AN: 152124 Hom.: 8041 Cov.: 32 AF XY: 0.304 AC XY: 22601 AN XY: 74360

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.283

Alfa AF: 0.278 Hom.: 6048

Bravo AF: 0.298

Asia WGS AF: 0.639 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1897604; hg19: chr19-51447954;